Our laboratory has been instrumental in elucidating the presence and clinical significance of antibody directed against antigens that are represented on vascular endothelial cells and are not represented to T cells, B cells, or renal cells, and therefore, this antigen system does not appear to be HLA-A, -B, -C, or DRw. Almost all renal allograft recipients who develop an antibody to vascular endothelial cells have irreversible graft rejection. Our studies strongly suggest that this antigen system is extremely important in the pathogenesis of graft rejection. However, much work remains in our understanding if this system is to be completed. Our work, and that of others, suggests that the "VE" antigen may be represented on the monocyte and therefore the cell specificity must be defined. Because of the high correlation between development of antibody to this antigen and graft rejection, it is essential that the number of specificities within this system be elucidated so we may type for this antigen with the hope of improving graft survival. The number of antigen specificities must be elucidated and monospecific typing sera developed. Essentially all patients who develop antibody to vascular endothelial cell antigens lose their grafts. A prospective study in patients developing antivascular endothelial cell antibody involving a change in the standard immunosuppressive regimen is clearly indicated, in an attempt to improve this almost uniform graft rejection. In summary, therefore, our laboratory has developed and evaluated the importance of the vascular endothelial cell antigen system in renal transplantation - observations that have been confirmed by others - and now wishes to extend this work so that we may, a) improve screening technique for this antibody, b) define the antigens within the system, c) improve the results in patients who become sensitized to vascular endothelial cell antigens, and d) further elucidate the specificity and ubiquity of this antigen system.